Treatment Strategies in PsA Management: Use of IL-17 Inhibitors

Key Takeaways:

• The signaling molecule interleukin-17 (IL-17) plays a major role in the pathogenesis of psoriatic arthritis (PsA)

• IL-17–producing cells are found in synovial fluid, psoriatic skin lesions, and the serum of individuals with PsA

• IL-17 is an important mediator of inflammation in patients with PsA

• The efficacy of IL-17 inhibitors has been demonstrated by the reported high—between 75% and 100%—clearing of psoriatic lesions with their use

• Improvements in psoriasis reported with the use of IL-17 inhibitors exceed those reported with the use of tumor necrosis factor (TNF) inhibitors

• Improvements in arthritis, however, are greater with the use of TNF inhibitors than with the use of IL-17 inhibitors

• According to the 2018 American College of Rheumatology/National Psoriasis Foundation Guideline for the Treatment of Psoriatic Arthritis, in patients with PsA, IL-17 inhibitors should be considered after two different TNF inhibitors have failed to control the disease

• Two agents are approved by the US Food and Drug Administration (FDA) for the treatment of PsA—secukinumab and ixekizumab—both of which are monoclonal antibodies that bind to IL-17 and block its ability to bind to its receptor

• A third agent that has been approved by the FDA blocks the IL-17A receptor and is indicated only for the treatment of psoriasis, not for the treatment of PsA

This transcript has been edited for clarity.

The signaling molecule interleukin-17 plays a central role in the pathogenesis of psoriatic arthritis. Interleukin-17–producing cells are found in synovial fluid, psoriatic skin lesions, and the serum of patients with psoriatic arthritis. Interleukin-17 receptors are increased on the surface of synovial cells. These and a variety of other findings indicate that interleukin-17 is an important mediator of inflammation in psoriatic arthritis and provide a rational basis for inhibition of interleukin-17 signaling as a treatment. 

There is strong evidence for the efficacy of interleukin-17 inhibitors. They produce dramatic improvement in psoriasis, exceeding that obtained with TNF inhibitors, often yielding as much as 75% to 100% clearing of psoriasis lesions. They also produce substantial benefit for psoriatic arthritis and do slow disease progression. 

However, unlike skin disease, improvement in arthritis does not typically exceed that obtained with TNF inhibitors. The 2018 American College of Rheumatology/National Psoriasis Foundation Guideline for the Treatment of Psoriatic Arthritis suggests interleukin-17 inhibitors be considered after two different TNF inhibitors have failed to control disease. In patients for whom control of psoriasis is the primary reason for treatment, earlier use of an interleukin-17 inhibitor might certainly be considered. 

Two drugs are approved by the Food and Drug Administration in the United States for treatment of psoriatic arthritis—secukinumab and ixekizumab. Both are monoclonal antibodies that bind to IL-17, blocking its ability to bind to its receptor. There is a third drug approved, which blocks the interleukin-17A receptor, but it is approved only for psoriasis and not for psoriatic arthritis. Indications for use of these drugs may well change as we gather additional data and experience with their use.